Topical Absorption of Glutathione–Cyclodextrin Nanoparticle Complex in Healthy Human Subjects Improves Immune Response against <i>Mycobacterium avium</i> Infection
Kayvan Sasaninia,
Melissa Kelley,
Arbi Abnousian,
Ali Badaoui,
Logan Alexander,
Nisar Sheren,
James Owens,
Shlok Rajurkar,
Brianna Razo-Botello,
Abraham Chorbajian,
Sonyeol Yoon,
Sanya Dhama,
Edith Avitia,
Cesar Ochoa,
Ray Yutani,
Vishwanath Venketaraman
Affiliations
Kayvan Sasaninia
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Melissa Kelley
Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA
Arbi Abnousian
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Ali Badaoui
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Logan Alexander
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Nisar Sheren
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
James Owens
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Shlok Rajurkar
Division of Biological Sciences, University of California Berkeley, Berkeley, CA 94720, USA
Brianna Razo-Botello
College of Natural and Agricultural Science, University of California Riverside, Riverside, CA 92521, USA
Abraham Chorbajian
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Sonyeol Yoon
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Sanya Dhama
Keck Science Department, Pitzer College, Claremont, CA 91711, USA
Edith Avitia
WesternU Center for Clinical Research, Western University of Health Sciences, Pomona, CA 91766, USA
Cesar Ochoa
WesternU Center for Clinical Research, Western University of Health Sciences, Pomona, CA 91766, USA
Ray Yutani
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Vishwanath Venketaraman
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
Glutathione (GSH) is an important intracellular antioxidant responsible for neutralizing reactive oxygen species (ROS). Our laboratory previously demonstrated that the oral administration of liposomal GSH improves immune function against mycobacterium infections in healthy patients along with patients with HIV and Type 2 diabetes. We aim to determine if the topical application of a glutathione–cyclodextrin nanoparticle complex (GSH-CD) confers a therapeutic effect against mycobacterium infections. In our study, healthy participants received either topical GSH-CD (n = 15) or placebo (n = 15) treatment. Subjects were sprayed four times twice a day for three days topically on the abdomen. Blood draws were collected prior to application, and at 1, 4, and 72 h post-initial topical application. GSH, malondialdehyde (MDA), and cytokine levels were assessed in the processed blood samples of study participants. Additionally, whole blood cultures from study participants were challenged with Mycobacterium avium (M. avium) infection in vitro to assess mycobacterium survival post-treatment. Topical GSH-CD treatment was observed to elevate GSH levels in peripheral blood mononuclear cells (PBMCs) and red blood cells and decrease MDA levels in PBMCs 72 h post-treatment. An increase in plasma IL-2, IFN-γ, IL-12p70, and TNF-α was observed at 72 h post-topical GSH-CD treatment. Enhanced mycobacterium clearance was observed at 4 h and 72 h post-topical GSH-CD treatment. Overall, topical GSH-CD treatment was associated with improved immune function against M. avium infection. The findings of this pilot study suggest GSH–cyclodextrin complex formulation can be used topically as a safe alternative mode of GSH delivery in the peripheral blood.
